Screening novel biomarkers for metabolic syndrome by profiling human plasma N-glycans in Chinese Han and Croatian populations.
N-glycans play an essential role in biological process and are associated with age, gender, and body mass parameters in Caucasian populations, whereas no study has been reported in Chinese populations. To investigate the correlation between N-glycan structures and metabolic syndrome (MetS) components, we conducted a population-based study in 212 Chinese Han individuals. The replication study was performed on 520 unrelated individuals from a Croatian island Korčula. The most prominent observation was the consistent positive correlations between different forms of triantennary glycans and negative correlations between glycans containing core-fucose with MetS components including BMI, SBP, DBP, and fasting plasma glucose (FPG) simultaneously. Significant differences in a number of N-glycan traits were also detected between normal and abnormal groups of BMI, BP, and FPG, respectively. In the multivariate analysis, the level of monosialylated glycans (structure loadings = -0.776) was the most correlated with the MetS related risk factors, especially with SBP (structure loadings = 0.907). Results presented here are showing that variations in the composition of the N-glycome in human plasma could represent the alternations of human metabolism and could be potential biomarkers of MetS.


Smoking and smoking cessation in relation to risk of diabetes in Chinese men and women: a 9-year prospective study of 0·5 million people.
In developed countries, smoking is associated with increased risk of diabetes. Little is known about the association in China, where cigarette consumption has increased (first in urban, then in rural areas) relatively recently. Moreover, uncertainty remains about the effect of smoking cessation on diabetes in China and elsewhere. We aimed to assess the associations of smoking and smoking cessation with risk of incident diabetes among Chinese adults. The prospective China Kadoorie Biobank enrolled 512 891 adults (59% women) aged 30-79 years during 2004-08 from ten diverse areas (five urban and five rural) across China. Participants were interviewed at study assessment clinics, underwent physical measurements, and had a non-fasting blood sample taken. Participants were separated into four categories according to smoking history: never-smokers, ever-regular smokers, ex-smokers, and occasional smokers. Incident diabetes cases were identified through linkage with diabetes surveillance systems, the national health insurance system, and death registries. All analyses were done separately in men and women and Cox regression was used to yield adjusted hazards ratios (HRs) for diabetes associated with smoking. 68% (n=134 975) of men ever smoked regularly compared with 3% (n=7811) of women. During 9 years' follow-up, 13 652 new-onset diabetes cases were recorded among 482 589 participants without previous diabetes. Among urban men, smokers had an adjusted HR of 1·18 (95% CI 1·12-1·25) for diabetes. HRs increased with younger age at first smoking regularly (1·12, 1·20, and 1·27 at ≥25 years, 20-24 years, and <20 years, respectively; p for trend=0·00073) and with greater amount smoked (1·11, 1·15, 1·42, and 1·63 for <20, 20-29, 30-39 and ≥40 cigarettes per day; p for trend<0·0001). Among rural men, similar, albeit more modest, associations were seen. Overall, HRs were more extreme at higher levels of adiposity. Among men who stopped by choice, there was no excess risk within 5 years of cessation, contrasting with those who stopped because of illness (0·92 [0·75-1·12] vs 1·42 [1·23-1·63]). Among the few women who ever smoked regularly, the excess risk of diabetes was significant (1·33 [1·20-1·47]). Among Chinese adults, smoking was associated with increased risk of diabetes, with no significant excess risk following voluntary smoking cessation. Wellcome Trust, Medical Research Council, British Heart Foundation, Cancer Research UK, Kadoorie Charitable Foundation, Ministry of Science and Technology, National Natural Science Foundation of China, and China Scholarship Council.


STUDIES IN RESUSCITATION: IV. THE RETURN OF FUNCTION IN THE CENTRAL NERVOUS SYSTEM AFTER TEMPORARY CEREBRAL ANAEMIA.
The experiments on cerebral anaemia have enabled us to duplicate, by an entirely different method, many of the results obtained by anatomical division or removal of parts of the central nervous system. In some respects the method of anaemia permits of greater precision than the method of division or excision, and avoids, in great measure, the disturbances due to the wound and to the hemorrhage caused by the latter method. The method of general anaemia, as Couty pointed out long ago, leaves something to be desired in the matter of exact localization, but this objection may be met, in some degree at least, by appropriate methods of investigation. It is desirable that the results obtained by the method of section should be duplicated by some other method in order to eliminate as much as possible the effects due to the irritation produced by the anatomical lesion. Our results show, as we believe, that, of the bulbar mechanisms studied, the respiratory is the most automatic, the vasomotor in part automatic, and the cardiac like the swallowing mechanism, almost wholly dependent upon afferent impulses for the arousal and discharge of its normal activity. The eye reflexes return during the resuscitation period in the animals in which the cerebral anaemia has not been too prolonged. The motor cortex loses its excitability during anaemia, but may regain it after the reëstablishment of the circulation. The pilomotor mechanism is disturbed during the spasms which occur at a certain stage in the resuscitation. The temperature falls during the occlusion period, but rises again, often to far above normal, in the days following the anaemia. So many disturbing factors, such as the violent muscular contractions during spasms, enter into the problem that it is impossible to say that there is an actual disturbance of the temperature regulating mechanism although we are inclined to believe that this is the case. All the senses return, following cerebral anaemia, but sight and hearing may afterwards fail without causing the death of the animal. The mental processes may return without any apparent deficiency, if the period of anaemia has been short. After longer occlusion, apparent insanity has been seen, and in one case, apparent total loss of mental processes occurred. The reflex excitability of the cord returns rather early in the resuscitation period. Reflexes from the anterior part of the cord first involve muscles on the same side as the stimulus, and later cross to involve muscles of the opposite side. The spinal cord sometimes falls into much the same condition as that following spinal transection, and the scratch reflex appears. Spinal transection, when these reflexes have appeared, does not produce shock. Practically all phenomena of spinal shock may be reproduced without section of the cord. We conclude, therefore, that spinal shock is due more to the cutting off of the reflex pathways through the higher centers of the nervous system than to the stimulation of inhibitory fibers by the anaemia.


No Effects of Black Tea on Cognitive Decline Among Older US Men: A Prospective Cohort Study.
Accumulating evidence supports the neuroprotective effects of bioactive compounds from tea leaves. There are limited data from black tea consumption populations. To determine whether black tea consumption is associated with cognitive decline among older men. We chose to study the association between black tea consumption and cognition using data from the Osteoporotic Fractures in Men (MrOS) cohort, which collected information on tea consumption at baseline and has repeatedly assessed cognitive function in 3,844 men aged 65+ years (mean = 72.4 years). We defined tea drinkers as those who drank black tea at least once per week and further grouped them into weekly drinkers and daily drinkers. Cognitive function was assessed at baseline and approximately 7 years later using the Modified Mini-Mental State Examination (3MSE). Multivariable logistic regression and linear regression models were constructed to assess the association between black tea consumption and risk of fast cognitive decline as a binary variable and change in 3MSE scores as continuous variable. Fast cognitive decline was defined as decline in 3MSE >1.5 standard deviation of mean change score. Models were adjusted for age, education level, and baseline cognitive scores. Weekly and daily black tea drinkers were 24.8% and 12.4% of the study cohort, respectively. Fast cognitive decline occurred in 243 (6.3%) participants. Tea consumption was not associated with risk of cognitive decline, nor was tea associated with cognitive decline measured by absolute change in 3MSE scores. There was no association of black tea consumption and cognitive decline among older men in the US.


An out-of-hours protocol for community palliative care: practitioners' perspectives.
Much of palliative care takes place in the patient's home. Out-of-hours service provision can be an area of concern. With the aim of improving this service, the former Calderdale and Kirklees Health Authority introduced an out-of-hours protocol for palliative care in the community. After 1 year the authors examined the experiences of primary care practitioners in using the protocol. Twenty district nurses and 15 GPs from 25 general practices in Calderdale, Huddersfield and North Kirklees took part in the study, which involved face-to-face group and individual telephone interviews. Practitioners felt that the out-of-hours protocol had made a positive contribution to palliative care in the community and that the out-of-hours handover form played a key role in improving communications and the coordination of services. For many participants, the protocol encouraged a more anticipatory approach to care and enabled better access to drugs and to specialist advice. The main areas of concern related to updating patient information on the handover forms, and to shortcomings in the support offered to carers. Future developments should address these issues. Although recognizing the dangers of generalization from research of this type, the findings offer encouragement to others considering similar schemes.


Dynamic contrast-enhanced MRI-based biomarkers of therapeutic response in triple-negative breast cancer.
To predict the response of breast cancer patients to neoadjuvant chemotherapy (NAC) using features derived from dynamic contrast-enhanced (DCE) MRI. 60 patients with triple-negative early-stage breast cancer receiving NAC were evaluated. Features assessed included clinical data, patterns of tumor response to treatment determined by DCE-MRI, MRI breast imaging-reporting and data system descriptors, and quantitative lesion kinetic texture derived from the gray-level co-occurrence matrix (GLCM). All features except for patterns of response were derived before chemotherapy; GLCM features were determined before and after chemotherapy. Treatment response was defined by the presence of residual invasive tumor and/or positive lymph nodes after chemotherapy. Statistical modeling was performed using Lasso logistic regression. Pre-chemotherapy imaging features predicted all measures of response except for residual tumor. Feature sets varied in effectiveness at predicting different definitions of treatment response, but in general, pre-chemotherapy imaging features were able to predict pathological complete response with area under the curve (AUC)=0.68, residual lymph node metastases with AUC=0.84 and residual tumor with lymph node metastases with AUC=0.83. Imaging features assessed after chemotherapy yielded significantly improved model performance over those assessed before chemotherapy for predicting residual tumor, but no other outcomes. DCE-MRI features can be used to predict whether triple-negative breast cancer patients will respond to NAC. Models such as the ones presented could help to identify patients not likely to respond to treatment and to direct them towards alternative therapies.


Risks of nutrigenomics and nutrigenetics? What the scientists say.
Nutrigenomics and nutrigenetics (hereafter NGx) have stimulated expectations for beneficial applications in public health and individuals. Yet, the potential achievability of such promise is not without socioethical considerations that challenge NGx implementation. This paper focuses on the opinions of NGx researchers about potential risks raised by NGx. The results of an online survey show that these researchers (n = 126) are fairly confident about the potential benefits of NGx, and that most downplay its potential risks. Researchers in this field do not believe that NGx will reconfigure foods as medication or transform the conception of eating into a health hazard. The majority think that NGx will produce no added burden on individuals to get tested or to remain compliant with NGx recommendations, nor that NGx will threaten individual autonomy in daily food choice. The majority of researchers do not think that NGx will lead to discrimination against and/or stigmatization of people who do not comply with NGx dietary recommendations. Despite this optimism among NGx researchers, we suggest that key risk factors raised by the socioethical context in which NGx applications will be implemented need to be considered.


Association of Nutritional Status with Cognitive Stage in the Elderly Korean Population: The Korean Brain Aging Study for the Early Diagnosis and Prediction of Alzheimer's Disease.
Epidemiological studies have suggested the presence of strong correlations among diet, lifestyle, and dementia onset. However, these studies have unfortunately had major limitations due to their inability to fully control the various potential confounders affecting the nutritional status. The purpose of the current study was to determine the nutritional status of participants in the Korean Brain Aging Study for the Early Diagnosis and Prediction of Alzheimer's Disease (KBASE) and to identify clinical risk factors for being at risk of malnutrition or being malnourished. Baseline data from 212 participants [119 cognitively unimpaired (CU), 56 with mild cognitive impairment (MCI), and 37 with dementia] included in the KBASE database were analyzed. All participants underwent a comprehensive cognitive test and MRI at baseline. The presence of malnutrition at baseline was measured by the Mini Nutritional Assessment score. We examined the cross-sectional relationships of clinical findings with nutritional status using multiple logistic regression applied to variables for which p<0.2 in the univariate analysis. Differences in cortical thickness according to the nutritional status were also investigated. After adjustment for demographic, nutritional, and neuropsychological factors, participants with dementia had a significantly higher odds ratio (OR) for being at risk of malnutrition or being malnourished than CU participants [OR=5.98, 95% CI=1.20-32.97] whereas participants with MCI did not (OR=0.62, 95% CI=0.20-1.83). Cortical thinning in the at-risk/malnutrition group was observed in the left temporal area. Dementia was found to be an independent predictor for the risk of malnutrition compared with CU participants. Our findings further suggest that cortical thinning in left temporal regions is related to the nutritional status.


The impact of supervision on stock management and adherence to treatment guidelines: a randomized controlled trial.
Ensuring the availability of essential drugs and using them appropriately are crucial if limited resources for health care are to be used optimally. While training of health workers throughout Zimbabwe in drug management (including stock management and rational drug use) resulted in significant improvements in a variety of drug use indicators, these achievements could not be sustained, and a new strategy was introduced based on the supervision of primary health care providers. This was launched in 1995 with a training course in supervisory skills for district pharmacy staff. In order to evaluate the impact of the supervision and the effectiveness of the training programme, adherence to standard treatment guidelines (STG) and stock management protocols was evaluated in a randomized controlled trial. The study compared three different groups of health facilities: those that received supervision for either use of STG (n = 23) or stock management (n = 21) - each facility acting as control for the other area of supervision - and a comparison group of facilities which received no supervision (n = 18). On-the-spot supervision by a specially trained pharmacy staff, based around identified deficiencies, took place at the start of the study and 3 months later. The evaluation compared performance on a variety of drug management indicators at baseline and 6-8 months after the second supervisory visit. The results of the study showed that, following supervision, overall stock management improved significantly when compared with the control and comparison groups. Similar improvements were demonstrated for adherence to STG, although the effect was confounded by other interventions. The study also showed that supervision has a positive effect on improving performance in areas other than those supervised, and demonstrated that pharmacy technicians with limited clinical skills can be trained to influence primary health care workers to positively improve prescribing practices. Allocating resources to supervision is likely to result in improved performance of health workers with regard to the rational use of essential drugs, resulting in improved efficiency and effectiveness.


Role of aquaporin-5 in gallbladder carcinoma.
Aquaporins (AQPs) are important in controlling bile formation. However, the exact role in human gallbladder carcinogenesis has not yet been defined. AQP-5-expressing gallbladder carcinoma (GBC) cell lines (NOZ) were transfected with anti-AQP-5 small interfering RNA (siRNA). Growth, migration, invasion assay, and drug susceptibility tests were performed. Next, microRNA (miRNA) expression was analyzed by miRNA oligo chip (3D-Gene®). AQP-5 and AQP-5-related miRNA target gene expressions were also analyzed using tissue microarray (TMA) in 44 GBC samples. Treatment with AQP-5 siRNA decreased cell proliferation, migration, and invasion. On the other hand, those cells increased IC50 of gemcitabine. By performing miRNA assays, miR-29b, -200a, and -21 were shown to be highly overexpressed in cells treated with AQP-5 siRNA NOZ. When focusing on miR-21, phosphatase and tensin homolog (PTEN) was found to be a target of miR-21. In the TMA, AQP-5/PTEN coexpression was significantly associated with the depth of invasion and MIB-1 index (p = 0.003, 0.010). Survival of patients with a high AQP-5/PTEN coexpression was longer than that of patients with a low coexpression (p = 0.003). Our result suggested that miR-21 and PTEN may contribute to the role of AQP-5 in GBC. AQP-5 and PTEN cascades are favorable biomarkers of GBC.


The relationship between smoking status and health-related quality of life among smokers who participated in a 1-year smoking cessation programme in Taiwan: a cohort study using the EQ-5D.
To assess the relationship between smoking status and health-related quality of life 1 year after participation in a smoking cessation programme in Taiwan. A cohort study of smokers who voluntarily participated in a smoking cessation programme with two follow-up assessments of smoking status via telephone interview, conducted 6 months and 1 year after finishing the smoking cessation programme. Hospitals and clinics providing smoking cessation services. A total of 3514 participants completed both telephone interviews, which represents a response rate of 64%. After the interviews, participants were divided into four groups according to their smoking status: (1) long-term quitters: participants who had quit tobacco use for 1 year; (2) short-term quitters: participants who had been smoking for at least 6 months and then quit tobacco for 6 months after participating in the programme; (3) relapsed smokers: participants who relapsed into tobacco use after ceasing tobacco use for 6 months; and (4) continuing smokers: participants who failed to quit smoking for at least 1 year, despite participating in the programme. The Outpatient Smoking Cessation Service of Taiwan provides counselling and pharmacotherapy to individuals seeking to quit smoking. The health-related quality of life of the participants was measured using an approved Chinese version of the EuroQol-5D-3L (EQ-5D-3L) descriptive system. After controlling for sex, age, education, marital status, job status, monthly income and disease status at baseline, our results revealed that long-term (OR=0.61 (0.48 to 0.77)) and short-term (OR=0.65 (0.54 to 0.79)) quitters experienced less anxiety and depression than did continuing smokers. Our study provides evidence to support claims that all quitters, regardless of whether they stop smoking for 6 months or 1 year, have better quality of life with regard to anxiety or depression.


Report on a single-topic conference on "Chronic viral hepatitis--strategies to improve effectiveness of screening and treatment".
The 2010 Institute of Medicine report on "Hepatitis and Liver Cancer" indicated that lack of knowledge and awareness about chronic hepatitis B (HBV) and C virus (HCV) infections and insufficient understanding about the extent and seriousness of this public health problem impeded current efforts to prevent and control hepatitis B and C. A single-topic conference was held in June 2011 to discuss strategies to improve the effectiveness of screening, care referral, and clinical management of chronic HBV and HCV infections with the ultimate goal of reducing morbidity and mortality from these infections. Various models that have been shown to improve hepatitis screening and effectiveness of hepatitis treatment in the community, including rural settings and populations that have traditionally been excluded due to comorbidities, were presented. Recent advances in laboratory testing, medical management, and new antiviral therapies will not decrease the burden of viral hepatitis if persons at risk for or who are living with viral hepatitis are not aware of the risks, have not been diagnosed, or have no access to care. Systematic changes in our health care delivery system and enhanced coordination of prevention and care services with partnerships between public health leaders and clinicians through education of the public and health care providers and linkage of infected persons with care and treatment services can increase the success of preventing viral hepatitis and the effectiveness of hepatitis treatment in the real world. Implementation of these changes is feasible and will require policy changes, coordination among government agencies, and collaboration between government agencies, health care providers, community organizations, and advocacy groups.


Morphology of early developing oligodendrocytes in the ventrolateral spinal cord of the chicken.
The oligodendroglial population includes Type I and II cells related to several thin axons, Type III cells with a few processes in relation to relatively thick axons and Type IV cells related to a single thick axon. This structural diversity of oligodendrocytes is accompanied by a molecular heterogeneity. In the chicken spinal cord, oligodendrocytes have begun to contact axons at embryonic day (E)10 and compact sheaths have appeared by E12. At the latter stage, most sheath-forming oligodendrocytes contact more than one axon. At E15, however, each sheath-forming cell seems to have developed a Schwann cell-like anatomy, being related to a single axon. Based on these findings, the present study examines more thoroughly the anatomy of early developing oligodendrocytes in the chicken spinal cord. Examination of slices immunostained with antibodies against the oligodendroglial marker O4 showed that a few positive cells are present at E6, after which the occurrence increases with age. At E12 most immunostained cells have two or more processes. At E15 however, dye-injected oligodendrocytes have developed a Type IV structure. Between E12 and E15, mean sheath length increases about 4x, from 50 microm to over 200 microm, while the length of the spinal cord increases 36% only. This indicates that early oligodendrocytes in chicken white matter develop a Type IV anatomy between E12 and E15 through an elimination of sheaths.


US medical schools and the rural family physician gender gap.
Women comprise increasing proportions of medical school graduates. They tend to choose primary care but are less likely than men to choose rural practice. This study used American Medical Association masterfile data on 1988-1996 medical school graduates to identify the US medical schools most successful at producing rural family physicians and general practitioners of both genders. The number of listed rural female family physician or general practitioner graduates among schools ranged from 0-27 (0% to 4.4% of each school's 1988-1996 graduates). There were approximately twice as many male as female rural family physicians and general practitioners. Publicly funded schools produced more rural female family physicians and general practitioners than their privately funded counterparts. Our findings suggest that a few schools, most of them public, may serve as models for schools that aim to train women who later enter rural practice.


Cutoff lensing: predicting catalytic sites in enzymes.
Predicting function-related amino acids in proteins with unknown function or unknown allosteric binding sites in drug-targeted proteins is a task of paramount importance in molecular biomedicine. In this paper we introduce a simple, light and computationally inexpensive structure-based method to identify catalytic sites in enzymes. Our method, termed cutoff lensing, is a general procedure consisting in letting the cutoff used to build an elastic network model increase to large values. A validation of our method against a large database of annotated enzymes shows that optimal values of the cutoff exist such that three different structure-based indicators allow one to recover a maximum of the known catalytic sites. Interestingly, we find that the larger the structures the greater the predictive power afforded by our method. Possible ways to combine the three indicators into a single figure of merit and into a specific sequential analysis are suggested and discussed with reference to the classic case of HIV-protease. Our method could be used as a complement to other sequence- and/or structure-based methods to narrow the results of large-scale screenings.


Unifying principles of calcium wave propagation - Insights from a three-dimensional model for atrial myocytes.
Atrial myocytes in a number of species lack transverse tubules. As a consequence the intracellular calcium signals occurring during each heartbeat exhibit complex spatio-temporal dynamics. These calcium patterns arise from saltatory calcium waves that propagate via successive rounds of diffusion and calcium-induced calcium release. The many parameters that impinge on calcium-induced calcium release and calcium signal propagation make it difficult to know a priori whether calcium waves will successfully travel, or be extinguished. In this study, we describe in detail a mathematical model of calcium signalling that allows the effect of such parameters to be independently assessed. A key aspect of the model is to follow the triggering and evolution of calcium signals within a realistic three-dimensional cellular volume of an atrial myocyte, but with low computational costs. This is achieved by solving the linear transport equation for calcium analytically between calcium release events and by expressing the onset of calcium liberation as a threshold process. The model makes non-intuitive predictions about calcium signal propagation. For example, our modelling illustrates that the boundary of a cell produces a wave-guiding effect that enables calcium ions to propagate further and for longer, and can subtly alter the pattern of calcium wave movement. The high spatial resolution of the modelling framework allows the study of any arrangement of calcium release sites. We demonstrate that even small variations in randomly positioned release sites cause highly heterogeneous cellular responses. This article is part of a Special Issue entitled: 13th European Symposium on Calcium.


The Retinoid Agonist Tazarotene Promotes Angiogenesis and Wound Healing.
Therapeutic angiogenesis is a major goal of regenerative medicine, but no clinically approved small molecule exists that enhances new blood vessel formation. Here we show, using a phenotype-driven high-content imaging screen of an annotated chemical library of 1,280 bioactive small molecules, that the retinoid agonist Tazarotene, enhances in vitro angiogenesis, promoting branching morphogenesis, and tubule remodeling. The proangiogenic phenotype is mediated by retinoic acid receptor but not retinoic X receptor activation, and is characterized by secretion of the proangiogenic factors hepatocyte growth factor, vascular endothelial growth factor, plasminogen activator, urokinase and placental growth factor, and reduced secretion of the antiangiogenic factor pentraxin-3 from adjacent fibroblasts. In vivo, Tazarotene enhanced the growth of mature and functional microvessels in Matrigel implants and wound healing models, and increased blood flow. Notably, in ear punch wound healing model, Tazarotene promoted tissue repair characterized by rapid ear punch closure with normal-appearing skin containing new hair follicles, and maturing collagen fibers. Our study suggests that Tazarotene, an FDA-approved small molecule, could be potentially exploited for therapeutic applications in neovascularization and wound healing.


New graduate employment in general practice: Perceptions of final-year nursing students.
This paper sought to investigate the perceptions of final-year nursing students regarding general practice nursing as a new graduate career path. General practice nurses have become increasingly important in providing community-based care, in response to the growing burden of chronic conditions and the ageing population. To sustain this workforce, there is a need to optimise strategies to promote a consistent supply of new graduate nurses. This qualitative descriptive study was undertaken within a sequential explanatory mixed methods project. Data were collected through semi-structured telephone interviews with sixteen final-year nursing students from five Australian universities. Interviews were analysed using thematic analysis. Four main themes were identified, namely; a) general practice is not a priority career path, b) opportunities for skills development and consolidation, c) perceptions of employment conditions, and d) transition support is limited. To meet current workforce needs in areas with increasing demand, nurse educators need to support undergraduate nursing students to explore a wide range of career pathways following graduation. Informed career choices and well-structured educational preparation during undergraduate education may be an effective strategy in building a sustainable future workforce in settings such as general practice.


Expanding the Map of Intrinsic and Extrinsic Aspirations Using Network Analysis and Multidimensional Scaling: Examining Four New Aspirations.
Life goals or aspirations can be distinguished as intrinsic or extrinsic, with different implications for well-being. In this study we used network analysis to reexamine this intrinsic-extrinsic distinction, illustrating how novel candidate aspirations can be mapped along this dimension using innovative methods. We identify four previously unexamined life aspirations, predicting that aspiring for power and social adherence would group with extrinsic goals, whereas aspiring for self-expression and mastery would group with intrinsic goals. In two samples (n = 196; n = 346) we analyze both the original life-goal variables and these novel aspirations using factor analysis, multidimensional scaling, circumplex modeling, and a network analysis using a graphical least absolute shrinkage and selection operator (glasso) to estimate the network structure of aspirations using EBIC. Replicating past intrinsic-extrinsic distinctions, all four methods further classified power and social adherence as extrinsic goals, and self-expression and mastery as intrinsic goals. The intrinsic-extrinsic distinction was also clearly visible in the network analysis. Finally, consistent with hypotheses, power and social adherence were unrelated to wellness indicators, whereas self-expression and mastery correlated positively with well-being indicators and negatively with ill-being indicators, supporting their hypothesized nature as extrinsic and intrinsic, respectively.


Capture heats up sharks.
Catch-and-release fishing is an important component of ecotourism industries and scientific research worldwide, but its total impact on animal physiology, health and survival is understudied for many species of fishes, particularly sharks. We combined biologging and blood chemistry to explore how this fisheries interaction influenced the physiology of two widely distributed, highly migratory shark species: the blue shark (Prionace glauca) and the tiger shark (Galeocerdo cuvier). Nineteen sharks were caught by drum line or rod-and-reel angling; subcutaneous body temperature measurements were taken immediately upon capture, with six individuals also providing subsequent subcutaneous body temperature measurements via biologging as they swam freely for several hours post-release. We found that short-term capture caused shark body temperature to increase significantly and rapidly, with increases of 0.6°C-2.7°C for blue sharks (mean, 1.2 ± 0.6°C) and 0.5°C-0.9°C for tiger sharks (mean, 0.7 ± 0.2°C) and with capture-induced heating rates of blue sharks averaging 0.3°C min-1 but as high as 0.8°C min-1. Blue shark body temperature was even higher deeper into the white muscle. These heating rates were three to eight times faster than maximum rates encountered by our biologging sharks swimming through thermally stratified waters and faster than most acute heating experiments conducted with ectotherms in laboratory experiments. Biologging data showed that body temperatures underwent gradual decline after release, returning to match water temperatures 10-40 mins post-release. Blood biochemistry showed variable lactate/glucose levels following capture; however, these concentrations were not correlated with the magnitude of body temperature increase, nor with body size or hooking time. These perturbations of the natural state could have immediate and longer-term effects on the welfare and ecology of sharks caught in catch-and-release fisheries and we encourage further study of the broader implications of this reported phenomenon.


Discrimination of dairy industry isolates of the Lactobacillus casei group.
Lactobacilli are a major part of the microflora of the gut and of many fermented dairy products, and are found in a variety of environments. Lactobacillus casei, Lactobacillus paracasei, Lactobacillus rhamnosus, and Lactobacillus zeae form a closely related taxonomic group within the facultatively heterofermentative lactobacilli. The classification and nomenclature of these bacteria are controversial. In this study, relationships between these species were investigated using type strains and dairy industry isolates examined with DNA-based techniques and conventional carbohydrate use tests. Carbohydrate use patterns gave poor discrimination of some species, but DNA PCR using specific primers targeted to sequences of the 16S rRNA gene discriminated 4 types consistent with the currently recognized species. Pulsed-field agarose gel electrophoresis of chromosomal NotI restriction fragments identified 18 different band patterns from 21 independent Lactobacillus isolates and confirmed the identity of L. casei strains from 2 culture collections (CSCC 5203 and ASCC 290), both representing the type strain of L. casei. Some isolates were reclassified as L. rhamnosus, suggesting that the prevalence of L. rhamnosus as a natural component of the microflora of dairy foods and dairy environments has previously been underestimated. These methods can provide a practical basis for discrimination of the species and identification of individual industrial strains.


Performances of endoscopic holography with a multicore optical fiber.
A holographic setup that involves the use of a multicore optical fiber as an in situ recording medium has been developed. The hologram is transmitted to a CCD camera for electronic processing, and the image is reconstructed numerically, providing more flexibility to the holographic process. The performances of this imaging system have been evaluated in terms of the resolution limit and robustness relative to noise. The experimental cutoff frequency has been measured experimentally over a range of observation distances (4-10 mm) and presents a very good agreement with the predictions made by simulation. The system features a resolution of 5-µm objects for a 4-mm observation distance. The different sources of noise have been analyzed, and their influence on resolution has been proved to be nonrelevant.


Extraordinary optical properties in the subwavelength metallodielectric free-standing grating.
In this paper, we present a free-standing metallodielectric grating structure that can achieve multiple transmission dips and peaks at normal incidence over the visible spectrum. The amount of dips and peaks can be adjusted by the thickness of dielectric film. In our proposed structure, there are three types of resonance modes supported: Surface plasmon polarition (SPP) at horizontal metal/dielectric interface, vertical cavity mode in the metal slits, and guide mode in the dielectric film. Physically the coupling and resonant interactions among these modes lead to the generation of dips and peaks in the transmission spectrum. The transmission peaks is further interpreted by using Fano resonance. More surprisingly, the simultaneous excitation of three types of resonance modes can enhance the field distribution, which results in unexpected nearly perfect absorption in such simple structure. Moreover, compared to other absorption peaks, this high absorption peak originates from that guide mode resonance in the dielectric film inhibits transmission induced by cavity mode resonance in the metal slits. These results can be used in the design of many photonics components.


Toward an ecologically meaningful view of resource stoichiometry in DOM-dominated aquatic systems.
Research on nutrient controls of planktonic productivity tends to focus on a few standard fractions of inorganic or total nitrogen (N) and phosphorus (P). However, there is a wide range in the degree to which land-derived dissolved organic nutrients can be assimilated by biota. Thus, in systems where such fractions form a majority of the macronutrient resource pool, including many boreal inland waters and estuaries, our understanding of bacterio- and phytoplankton production dynamics remains limited. To adequately predict aquatic productivity in a changing environment, improved standard methods are needed for determining the sizes of active (bioavailable) pools of N, P and organic carbon (C). A synthesis of current knowledge suggests that variation in the C:N:P stoichiometry of bioavailable resources is associated with diverse processes that differentially influence the individual elements across space and time. Due to a generally increasing organic nutrient bioavailability from C to N to P, we hypothesize that the C:N and N:P of bulk resources often vastly overestimates the corresponding ratios of bioavailable resources. It is further proposed that basal planktonic production is regulated by variation in the source, magnitude and timing of terrestrial runoff, through processes that have so far been poorly described.


Maintenance of the relative proportion of oligodendrocytes to axons even in the absence of BAX and BAK.
Highly purified oligodendroglial lineage cells from mice lacking functional bax and bak genes were resistant to apoptosis after in-vitro differentiation, indicating an essential role of the intrinsic apoptotic pathway in apoptosis of oligodendrocytes in the absence of neurons (axons) and other glial cells. These mice therefore provide a valuable tool with which to evaluate the significance of the intrinsic apoptotic pathway in regulating the population sizes of oligodendrocytes and oligodendroglial progenitor cells. Quantitative analysis of the optic nerves and the dorsal columns of the spinal cord revealed that the absolute numbers of mature oligodendrocytes immunolabeled for aspartoacylase and adult glial progenitor cells expressing NG2 chondroitin sulfate proteoglycan were increased in both white matter tracts of adult bax/bak-deficient mice and, to a lesser extent, bax-deficient mice, except that there was no increase in NG2-positive progenitor cells in the dorsal columns of these strains of mutant mice. These increases in mature oligodendrocytes and progenitor cells in bax/bak-deficient mice were unexpectedly proportional to increases in numbers of axons in these white matter tracts, thus retaining the oligodendroglial lineage to axon ratios of at most 1.3-fold of the physiological numbers. This is in contrast to the prominent expansion in numbers of neural precursor cells in the subventricular zones of these adult mutant mice. Our study indicates that homeostatic control of cell number is different for progenitors of the oligodendroglial and neuronal lineages. Furthermore, regulatory mechanism(s) operating in addition to apoptotic elimination through the intrinsic pathway, appear to prevent the overproduction of highly mitotic oligodendroglial progenitor cells.


A comparison of fish oil or corn oil supplements in hyperlipidemic subjects with NIDDM.
To examine the effects on blood lipids and glycemic control of fish oil and corn oil supplementation at two levels in subjects with hyperlipidemia and non-insulin-dependent diabetes mellitus (NIDDM). Forty subjects (18 men and 22 women; aged 53.9 +/- 7.0 years) with NIDDM and hyperlipidemia were randomly assigned to one of four treatment groups: 9 g of fish oil, 18 g of fish oil, 9 g of corn oil, or 18 g of corn oil daily supplementation for 12 weeks. The level of oil supplements (9 g compared with 18 g) did not have a significant effect within each oil group on glycemic control and lipids. Significant differences (P < 0.05) in lipids were found when the 9-g and 18-g groups were combined. In subjects consuming fish oil, plasma very-low-density lipoprotein (VLDL) cholesterol (P = 0.0001), plasma triglyceride (TG) (P = 0.0001), and plasma VLDL TGs (P = 0.02 at 6 weeks and P = 0.0001 at 12 weeks) were significantly lowered compared with subjects consuming corn oil. Plasma VLDL cholesterol increased across time in the corn oil group (P = 0.04). Plasma low-density lipoprotein (LDL) cholesterol was temporarily increased (P = 0.008) in the fish oil group at 6 weeks, but the effect was no longer present at 12 weeks. No significant differences between fish oil- or corn oil-supplemented diets were found in total plasma cholesterol, high-density lipoprotein cholesterol, fasting plasma glucose, glycosylated HbA1c, weight, and blood pressure. In this study, fish oil supplementation improved plasma VLDL cholesterol, VLDL TGs, and total TGs while having a transient deterioration in LDL cholesterol in subjects with NIDDM. Furthermore, fish oil supplementation had no significant deleterious effect on glycemic control.


Socioeconomic status and lung cancer: unraveling the contribution of genetic admixture.
We examined the relationship between genetic ancestry, socioeconomic status (SES), and lung cancer among African Americans and Latinos. We evaluated SES and genetic ancestry in a Northern California lung cancer case-control study (1998-2003) of African Americans and Latinos. Lung cancer case and control participants were frequency matched on age, gender, and race/ethnicity. We assessed case-control differences in individual admixture proportions using the 2-sample t test and analysis of covariance. Logistic regression models examined associations among genetic ancestry, socioeconomic characteristics, and lung cancer. Decreased Amerindian ancestry was associated with higher education among Latino control participants and greater African ancestry was associated with decreased education among African lung cancer case participants. Education was associated with lung cancer among both Latinos and African Americans, independent of smoking, ancestry, age, and gender. Genetic ancestry was not associated with lung cancer among African Americans. Findings suggest that socioeconomic factors may have a greater impact than genetic ancestry on lung cancer among African Americans. The genetic heterogeneity and recent dynamic migration and acculturation of Latinos complicate recruitment; thus, epidemiological analyses and findings should be interpreted cautiously.


Projections of the lateral reticular nucleus to the cochlear nucleus in rats.
The lateral reticular nucleus (LRN) resides in the rostral medulla and caudal pons, is implicated in cardiovascular regulation and cranial nerve reflexes, and gives rise to mossy fibers in the cerebellum. Retrograde tracing data revealed that medium-sized multipolar cells from the magnocellular part of the LRN project to the cochlear nucleus (CN). We sought to characterize the LRN projection to the CN using BDA injections. Anterogradely labeled terminals in the ipsilateral CN appeared as boutons and mossy fibers, and were examined with light and electron microscopy. The terminal field in the CN was restricted to the granule cell domain (GCD), specifically in the superficial layer along the anteroventral CN and in the granule cell lamina. Electron microscopy showed that the smallest LRN boutons formed 1-3 synapses, and as boutons increased in size, they formed correspondingly more synapses. The largest boutons were indistinguishable from the smallest mossy fibers, and the largest mossy fiber exhibited 15 synapses. Synapses were asymmetric with round vesicles and formed against thin dendritic profiles characterized by plentiful microtubules and the presence of fine filopodial extensions that penetrated the ending. These structural features of the postsynaptic target are characteristic of the terminal dendritic claw of granule cells. LRN projections are consistent with known organizational principles of non-auditory inputs to the GCD.


Analysis of a symbiosis-specific cytochrome P450 homolog in Rhizobium sp. BR816.
Sequence analysis of the DNA region upstream of nodO in Rhizobium sp. BR816 revealed an open reading frame in which the deduced amino acid sequence shows homology with cytochrome P450. Because the BR816 P450 homolog shows 73% amino acid similarity with CYP127A1(Y4vG), which is identified on the symbiotic plasmid of Rhizobium sp. NGR234, it is named CYP127A2. Transcriptional analysis of CYP127A2 revealed high expression in bacteroids, whereas no or hardly any expression was observed under free-living conditions. Low-level, free-living expression, however was noticed when cells were grown microoxically at acid pH levels. A number of possible substrates that may induce P450 gene expression were analyzed, but only the addition of short-chain alcohols to cultures slightly increased CYP127A2 expression. High levels of CYP127A2 expression observed in bacteroids of a nifH mutant strain, which formed non-fixing nodules on bean, indicated that the genuine substrate for CYP127A2 is not a metabolite resulting from N2-fixation. Nevertheless, expression analysis pointed to a NifA- and sigma54-dependent transcription.


Engaging media in communicating research on sexual and reproductive health and rights in sub-Saharan Africa: experiences and lessons learned.
The mass media have excellent potential to promote good sexual and reproductive health outcomes, but around the world, media often fail to prioritize sexual and reproductive health and rights issues or report them in an accurate manner. In sub-Saharan Africa media coverage of reproductive health issues is poor due to the weak capacity and motivation for reporting these issues by media practitioners. This paper describes the experiences of the African Population and Health Research Center and its partners in cultivating the interest and building the capacity of the media in evidence-based reporting of reproductive health issues in sub-Saharan Africa. The paper utilizes a case study approach based primarily on the personal experiences and reflections of the authors (who played a central role in developing and implementing the Center's communication and policy engagement strategies), a survey that the Center carried out with science journalists in Kenya, and literature review. The African Population and Health Research Center's media strategy evolved over the years, moving beyond conventional ways of communicating research through the media via news releases and newspaper stories, to varying approaches that sought to inspire and build the capacity of journalists to do evidence-based reporting of reproductive health issues. Specifically, the approach included 1) enhancing journalists' interest in and motivation for reporting on reproductive health issues through training and competitive grants for outstanding reporting ; 2) building the capacity of journalists to report reproductive health research and the capacity of reproductive health researchers to communicate their research to media through training for both parties and providing technical assistance to journalists in obtaining and interpreting evidence; and 3) establishing and maintaining trust and mutual relationships between journalists and researchers through regular informal meetings between journalists and researchers, organizing field visits for journalists, and building formal partnerships with professional media associations and individual journalists. Our experiences and reflections, and the experiences of others reviewed in this paper, indicate that a sustained mix of strategies that motivate, strengthen capacity of, and build relationships between journalists and researchers can be effective in enhancing quality and quantity of media coverage of research.


Italian Society of Rheumatology recommendations for the management of gout.
Gout is the most common arthritis in adults. Despite the availability of valid therapeutic options, the management of patients with gout is still suboptimal. The Italian Society of Rheumatology (SIR) aimed to update, adapt to national contest and disseminate the 2006 EULAR recommendations for the management of gout. The multidisciplinary group of experts included rheumatologists, general practitioners, internists, geriatricians, nephrologists, cardiologists and evidence-based medicine experts. To maintain consistency with EULAR recommendations, a similar methodology was utilized by the Italian group. The original propositions were translated in Italian and priority research queries were identified through a Delphi consensus approach. A systematic search was conducted for selected queries. Efficacy and safety data on drugs reported in RCTs were combined in a meta-analysis where feasible. The strength of recommendation was measured by utilising the EULAR ordinal and visual analogue scales. The original 12 propositions were translated and adapted to Italian context. Further evidences were collected about the role of diet in the non-pharmacological treatment of gout and the efficacy of oral corticosteroids and low-dose colchicine in the management of acute attacks. Statements concerning uricosuric treatments were withdrawn and replaced with a proposition focused on a new urate lowering agent, febuxostat. A research agenda was developed to identify topics still not adequately investigated concerning the management of gout. The SIR has developed updated recommendations for the management of gout adapted to the Italian healthcare system. Their implementation in clinical practice is expected to improve the management of patients with gout.


Gene clusters and the HLA system.
The major human histocompatibility, or HLA system, is now known to include a number of closely linked loci controlling cell surface specificities, components of the complement system and immune response. Three loci, HLA-A, B and C, control serological determinants found on nearly all cells; a fourth locus, HLA-D, codes for determinants controlling the mixed lymphocyte culture reaction that are present only on B lymphocytes and monocytes. The products of the HLA-A, B and C loci are very similar to each other, as expected if they have arisen by duplication from a common ancestor. The HLA-D products however, show no homology with these and each in turn is different from the complement components (C2, C4 and Bf) coded for in the HLA region. If this complex genetic region has arisen by a series of duplications, one must explain how four different structural gene products can arise from a single duplicated nucleic acid sequence. Different proteins could be translated from the same nucleotide sequence through the use either of different reading frames or of different, not necessarily adjacent, parts of a sequence in different combinations. It seems likely that the general organization of the genetic material of higher organisms is into clusters of duplicated genes like the HLA region and that the numbers of such clusters, rather than the number of individual genes, reflects the genetic complexity of higher organisms.


Diagnosis of footrot in goats: application of ELISA tests for response to antigens of Dichelobacter nodosus.
Goats are an important natural host for footrot and are infected with Dichelobacter nodosus that have virulence characteristics similar to those of sheep strains. However, the humoral response of goats to D. nodosus antigens and the possibility of a serological diagnosis of footrot in goats have not been studied. With the aim of evaluating a diagnostic ELISA test, we investigated the primary immune response of goats to experimental and natural infection, the memory response in recovered animals, and the transfer and persistence of colostral antibodies in kids. Footrot stimulated the goat's immune system and, as in sheep, under-running lesions were the primary stimulus for production of anti-D. nodosus antibodies. The immune response could be detected in ELISA using either fimbrial or outer membrane protein (KSCN) antigens of D. nodosus. Antibody titres resulting from infection declined quickly after recovery and reached pre-infection levels within 3-4 months. Previously affected animals, however, mounted a memory response when injected with purified D. nodosus antigens. Antibody levels attained after anamnestic challenge were correlated with the maximum levels attained during infection, and were therefore indicative of the infection status. Anti-D. nodosus antibodies were also transferred to kids via colostrum, but these antibodies did not persist and therefore were unlikely to interfere with the diagnostic ELISA after 3 months of age. Though these ELISA tests were highly specific, their sensitivity was rather low. Therefore, they are only suitable for a herd diagnosis of footrot in goats and are dependent on the development of advanced under-running infections in a proportion of affected goats.


Effects of in vivo exposure to GSM-modulated 900 MHz radiation on mouse peripheral lymphocytes.
The aim of this study was to evaluate whether daily whole-body exposure to 900 MHz GSM-modulated radiation could affect spleen lymphocytes. C57BL/6 mice were exposed 2 h/day for 1, 2 or 4 weeks in a TEM cell to an SAR of 1 or 2 W/kg. Untreated and sham-exposed groups were also examined. At the end of the exposure, mice were killed humanely and spleen cells were collected. The number of spleen cells, the percentages of B and T cells, and the distribution of T-cell subpopulations (CD4 and CD8) were not altered by the exposure. T and B cells were also stimulated ex vivo using specific monoclonal antibodies or LPS to induce cell proliferation, cytokine production and expression of activation markers. The results did not show relevant differences in either T or B lymphocytes from mice exposed to an SAR of 1 or 2 W/kg and sham-exposed mice with few exceptions. After 1 week of exposure to 1 or 2 W/kg, an increase in IFN-gamma (Ifng) production was observed that was not evident when the exposure was prolonged to 2 or 4 weeks. This suggests that the immune system might have adapted to RF radiation as it does with other stressing agents. All together, our in vivo data indicate that the T- and B-cell compartments were not substantially affected by exposure to RF radiation and that a clinically relevant effect of RF radiation on the immune system is unlikely to occur.


Typologies of Family Functioning and 24-h Movement Behaviors.
Research on the importance of the family environment on children's health behaviors is ubiquitous, yet critical gaps in the literature exist. Many studies have focused on one family characteristic and have relied on variable-centered approaches as opposed to person-centered approaches (e.g., latent profile analysis). The purpose of the current study was to use latent profile analysis to identify family typologies characterized by parental acceptance, parental monitoring, and family conflict, and to examine whether such typologies are associated with the number of movement behavior recommendations (i.e., physical activity, screen time, and sleep) met by children. Data for this cross-sectional observational study were part of the baseline data from the Adolescent Brain Cognitive Development (ABCD) study. Data were collected across 21 study sites in the United States. Participants included 10,712 children (female = 5143, males = 5578) aged 9 and 10 years (M = 9.91, SD = 0.62). Results showed that children were meaningfully classified into one of five family typologies. Children from families with high acceptance, medium monitoring, and medium conflict (P2; OR = 0.54; 95% CI, 0.39-0.76); high acceptance, medium monitoring, and high conflict (P3; OR = 0.28; 95% CI, 0.20, 0.40); low acceptance, low monitoring, and medium conflict (P4; OR = 0.24; 95% CI, 0.16, 0.36); and medium acceptance, low monitoring, and high conflict (P5; OR = 0.19; 95% CI, 0.12-0.29) were less likely to meet all three movement behavior recommendations compared to children from families with high acceptance, high monitoring, and low conflict (P1). These findings highlight the importance of the family environment for promoting healthy movement behaviors among children.


Effect of glare on simple reaction time.
We systematized the study of the effect of glare on reaction time (RT), for visual conditions similar to the ones found during night driving: Mesopic range of adaptation (0.14 cd/m2), glare levels of the order of those produced by car headlights (E(G)=15, 60 lx), suprathreshold luminance contrasts, and a variety of spatial frequencies covering the selected range of visibility (1, 2, 4, and 8 c/deg). We found that for the no-glare situation, RT increases with decreasing contrast and increasing spatial frequency, which agrees with previous findings. When data are plotted as a function of the inverse of contrast, RT varies linearly, with k--the RT-contrast factor of Pieron's law--representing the slope of the lines. The effect of glare on RT is an increase in the slope of these lines. This effect is different for each spatial frequency, which cannot be accounted for in the classic approach considering that glare can be replaced by a single veiling luminance. We show that the effect of glare on RT must be modeled by an equivalent glare luminance that depends on spatial frequency.


Phenotypic comparison of clinical and plant-beneficial strains of Pantoea agglomerans.
Certain strains of Pantoea are used as biocontrol agents for the suppression of plant diseases. However, their commercial registration is hampered in some countries because of biosafety concerns. This study compares clinical and plant-beneficial strains of P. agglomerans and related species using a phenotypic analysis approach in which plant-beneficial effects, adverse effects in nematode models, and toxicity were evaluated. Plant-beneficial effects were determined as the inhibition of apple fruit infection by Penicillium expansum and apple flower infection by Erwinia amylovora. Clinical strains had no general inhibitory activity against infection by the fungal or bacterial plant pathogens, as only one clinical strain inhibited P. expansum and three inhibited E. amylovora. By contrast, all biocontrol strains showed activity against at least one of the phytopathogens, and three strains were active against both. The adverse effects in animals were evaluated in the plant-parasitic nematode Meloidogyne javanica and the bacterial-feeding nematode Caenorhabditis elegans. Both models indicated adverse effects of the two clinical strains but not of any of the plant-beneficial strains. Toxicity was evaluated by means of hemolytic activity in blood, and genotoxicity with the Ames test. None of the strains, whether clinical or plant-beneficial, showed any evidence of toxicity.


Longitudinal study exploring factors associated with neck/shoulder pain at 52 years of age.
To investigate the ability of work-related measurements, body composition, physical activity, and fitness levels to predict neck/shoulder pain (upper body pain, UBP) at the age of 52 years. Another aim was to investigate the cross-sectional relationships between UBP, work-related factors, and individual factors at the age of 52 years. We followed a randomly selected cohort of 429 adolescents that was recruited in 1974 (baseline), when they were 16 years old. The participants completed physical fitness tests, questions about sociodemographic and lifestyle factors at 16, 34, and 52 years of age, and questions about work-related factors and pain in the follow-ups. Logistic regression analyses were used to examine the associations between UBP and the other variables. Univariate logistic regression analyses showed that high body mass index and the work-related factors, low control, and low social support at the age of 34 years were related to UBP at the age of 52 years. For social support, there was an interaction between men and women where the relationship between low social support and the experience of pain was more evident for women. Among women, body mass index and social support remained significantly related in the multivariate analyses. For men, social support remained significantly related. Cross-sectional relationships at the age of 52 differed from the longitudinal in the sense that measures of joint flexibility and work posture were also significantly associated with UBP. The fact that the cross-sectional differed from the longitudinal relationships strengthens the importance of performing longitudinal studies when studying factors that might influence the initiation of pain. UBP preventative measures might need to include both lifestyle (such as dietary habits and physical activity to ensure that the individuals are not becoming overweight) and work-related factors such as social support.


Single instillation of mitomycin C reduces 1st year recurrence following transurethral resection of non-muscle invasive bladder cancer.
To study the impact of single instillation of 40 mg Mitomycin C (MMC-40) within first hour of transurethral resection (TUR), on first year recurrence of non-muscle invasive bladder cancer. In this study of two groups of patients with similar demographics and tumour profile were compared to assess first year tumour recurrence pattern. Group A received MMC-40 within 30 minutes of TUR. Group B patients only had TUR of bladder tumour. Patients' charts were reviewed for demographic profile, preoperative diagnosis and imaging used, cytological work up, tumour profile both during cystoscopy and imaging used, patients records were also reviewed for all subsequent check cystoscopies for recurrence. Any adjuvant treatments like intravesical chemo/immunotherapy etc. were also noted. The results were analysed using a commercially available statistical package, SPSS. The level of significance was < or = 0.05. There were 29 and 46 patients in group A and B respectively. The demographic profile in terms of age, gender distribution, tumour characteristics (size, site, multiplicity) and pathological evaluation including, tumour grade and presence of carcinoma in situ were similar (p < 0.4 and p < 0.5) respectively. The first year recurrence rate in group A was 15% whereas it was 37.4% in group B (p < 0.04). The first year recurrence rate is significantly decreased if MMC-40 is instilled following TUR. MMC-40 is safe and cost effective. Most low grade, low volume tumours would not require any further treatment if MMC-40 is given immediately following TUR.


Undernutrition during the gestation and suckling periods does not cause any loss of pyramidal neurons in the CA2-CA3 region of the rat hippocampus.
The total number of hippocampal pyramidal cells in the CA2-CA3 region are reported to be unaffected by undernutrition during the gestation period. We hypothesised that this may not be the case in animals subjected to a lengthier period of undernutrition. Wistar rats were undernourished from conception until 21 post-natal days-of-age and killed for examination at 21 and 62 days-of-age. There were between 180-212 thousand pyramidal cells in control animals at both 21 and 62 days of age. Twenty-one-day-old undernourished rats had about 152 thousand such cells and this increased to about 206 thousand by 62 days-of-age. Analysis of variance tests on these data revealed a significant main effect of age but no group or interaction effects. Our experiments, therefore, confirm that these hippocampal pyramidal neurons are relatively spared the adverse effects of undernutrition during early life, even when this is extended to include both the gestation and suckling periods.


Suppression of Etk/Bmx protects against ischemic brain injury.
Etk/Bmx (epithelial and endothelial tyrosine kinase, also known as BMX), a member of the Tec (tyrosine kinase expressed in hepatocellular carcinoma) family of protein-tyrosine kinases, is an important regulator of signal transduction for the activation of cell growth, differentiation, and development. We have previously reported that activation of Etk leads to apoptosis in MDA-MB-468 cells. The purpose of this study was to examine the role of Etk in neuronal injury induced by H(2)O(2) or ischemia. Using Western blot analysis and immunohistochemistry, we found that treatment with H(2)O(2) significantly enhanced phosphorylation of Etk and its downstream signaling molecule Stat1 in primary cortical neurons. Inhibiting Etk activity by LFM-A13 or knocking down Etk expression by a specific shRNA increased the survival of primary cortical neurons. Similarly, at 1 day after a 60-min middle cerebral artery occlusion (MCAo) in adult rats, both phosphorylated Etk and Stat1 were coexpressed with apoptotic markers in neurons in the penumbra. Pretreatment with LFM-A13 or an adenoviral vector encoding the kinase deletion mutant Etkk attenuated caspase-3 activity and infarct volume in ischemic brain. All together, our data suggest that Etk is activated after neuronal injury. Suppressing Etk activity protects against neurodegeneration in ischemic brain.


Four years of surveillance of recent HIV infections at country level, France, mid 2003 - 2006: experience and perspectives.
New systems of surveillance to better monitor the dynamics of HIV are needed. A national surveillance of new HIV diagnoses which included the collection of dried serum spots (DSS) to identify recent infections (<6 months) using an EIA-RI assay was implemented in 2003 in France. The collection of DSS is based on the voluntary participation by both patients and microbiologists. Multivariate analysis was used to identify factors associated with recent infection (RI). Between July 2003 and December 2006, 14,155 cases newly diagnosed for HIV were reported. A minority of patients refused the collection of DSS (3.3%) and the rate of participation of laboratories was 80%. The test was performed for 10,855 newly diagnosed HIV cases, the overall proportion of RI was 23.1% (95% CI, 22.3%-23.9%). The proportion of RI was higher among men who have sex with men (MSM) (42.8%) than among heterosexuals (16.3%). Among heterosexuals, it varied by current nationality: 27% among French versus 8.4% among Africans. The risk of RI was greater for MSM (aOR=1.8), those of French nationality (aOR=3.9), those with high-economic status (aOR=1.2), those tested after a risk exposure (aOR=1.4), those tested for HIV three or more times during their lifetime (aOR=2.5). The risk of RI decreased with age. A nation-wide implementation of RI monitoring is feasible. The information on RI is very useful for renewing prevention messages, particularly among population in which HIV transmission is on going, such as MSM.


Programming hierarchical self-assembly of colloids: matching stability and accessibility.
Encoding hierarchical self-assembly in colloidal building blocks is a promising bottom-up route to high-level structural complexity often observed in biological materials. However, harnessing this promise faces the grand challenge of bridging hierarchies of multiple length- and time-scales, associated with structure and dynamics respectively along the self-assembly pathway. Here we report on a case study, which examines the kinetic accessibility of a series of hollow spherical structures with a two-level structural hierarchy self-assembled from charge-stabilized colloidal magnetic particles. By means of a variety of computational methods, we find that for a staged assembly pathway, the structure, which derives the strongest energetic stability from the first stage of assembly and the weakest from the second stage, is most kinetically accessible. Such a striking correspondence between energetics and kinetics for optimal design principles should have general implications for programming hierarchical self-assembly pathways for nano- and micro-particles, while matching stability and accessibility.


Aluminium-adjuvanted vaccines transiently increase aluminium levels in murine brain tissue.
Aluminium is widely used as an adjuvant in human vaccines, and children can often receive up to 3.75 mg of parenteral aluminium during the first six months of life. We show that intraperitoneal injection of aluminium adsorbed vaccines into mice causes a transient rise in brain tissue aluminium levels peaking around the second and third day after injection. This rise is not seen in the saline control group of animals or with vaccine not containing aluminium. It is likely that aluminium is transported to the brain by the iron-binding protein transferrin and enters the brain via specific transferrin receptors.


Evaluation of the rapid MGIT TBc identification test for culture confirmation of Mycobacterium tuberculosis complex strain detection.
A culture confirmation test for the detection of Mycobacterium tuberculosis complex strains that uses a lateral-flow immunochromatographic assay to detect the MPB64 antigen, the MGIT TBc identification (TBc ID) test, has been developed. We evaluated the performance of the TBc ID test in the detection of the M. tuberculosis complex in 222 primary-positive liquid cultures. We compared these results to those of nucleic acid-based identification and conventional biochemical tests. The validity of the TBc ID test was determined, and all of the nontuberculous mycobacteria (NTM) and Nocardia species tested were found to be negative. The detection limit of the TBc ID test was 5 × 10(5) CFU/ml, and for IS6110 real-time PCR it was 5 CFU/ml. All of the M. tuberculosis and M. africanum cultures were found to be positive, while M. bovis and M. bovis BCG cultures were negative. With the exception of 1 contaminated culture, the 221 culture-positive isolates contained 171 (77.5%) M. tuberculosis isolates, 39 (17.6%) NTM species, and 11 (5.0%) unidentified species. Two culture-positive isolates harbored a 63-bp deletion at position 196 of the mpb64 gene. The sensitivity, specificity, positive predictive values, and negative predictive values of the TBc ID test were 98.8, 100, 100, and 95.1%, respectively. Furthermore, the approximate turnaround time for real-time PCR was 4 h (including buffer and sample preparation), while for the TBc ID test it was less than 1 h. We suggest an algorithm for the primary identification of M. tuberculosis in liquid culture using the TBc ID test as an alternative to conventional subculture followed by identification using biochemical methods.


The n170 shows differential repetition effects for faces, objects, and orthographic stimuli.
Previous event-related potentials research has suggested that the N170 component has a larger amplitude to faces and words than to other stimuli, but it remains unclear whether it indexes the same cognitive processes for faces and for words. The present study investigated how category-level repetition effects on the N170 differ across stimulus categories. Faces, cars, words, and non-words were presented in homogeneous (1 category) or mixed blocks (2 intermixed categories). We found a significant repetition effect of N170 amplitude for successively presented faces and cars (in homogeneous blocks), but not for words and unpronounceable consonant strings, suggesting that the N170 indexes different underlying cognitive processes for objects (including faces) and orthographic stimuli. The N170 amplitude was significantly smaller when multiple faces or multiple cars were presented in a row than when these stimuli were preceded by a stimulus of a different category. Moreover, the large N170 repetition effect for faces may be important to consider when comparing the relative N170 amplitude for different stimulus categories. Indeed, a larger N170 deflection for faces than for other stimulus categories was observed only when stimuli were preceded by a stimulus of a different category (in mixed blocks), suggesting that an enhanced N170 to faces may be more reliably observed when faces are presented within the context of some non-face stimuli.


Roll, adhere, spread and contract: structural mechanics of platelet function.
Platelets are involved in life-sustaining processes such as hemostasis, wound healing, atherothrombosis and angiogenesis. Mechanical trauma to blood vessels causes platelet activation resulting in their adherence and clot formation at the damaged site, culminating in clot retraction and tissue repair. Two of the major players underlying this process are the cytoskeleton, i.e., actin and microtubules, and the membrane integrin receptors. Rare congenital bleeding disorders such as Glanzmann thrombasthenia and Bernard-Soulier syndrome are associated with genetic alterations of platelet surface receptors, also affecting the platelet cytoskeletal structure. In this review, we summarize the current knowledge about platelet structure and adhesion, and delve into the mechanical aspects of platelet function. Platelets lack a nucleus, and can thus provide a minimal model of a biological cell. New biophysical tools may help to scrutinize platelets anew and to extend the existing knowledge on cell biology.


Never mind the length, feel the quality: the impact of long-term epidemiological data sets on theory, application and policy.
Infectious diseases have been a prime testing ground for ecological theory. However, the ecological perspective is increasingly recognized as essential in epidemiology. Long-term, spatially resolved reliable data on disease incidence and the ability to test them using mechanistic models have been critical in this cross-fertilization. Here, we review some of the key intellectual developments in epidemiology facilitated by long-term data. We identify research frontiers at the interface of ecology and epidemiology and their associated data needs.


Transcriptional regulation of the human toll-like receptor 2 gene in monocytes and macrophages.
This report investigates the molecular basis for tissue-restricted and regulated expression of the pattern recognition receptor Toll-like receptor (TLR)2 in human monocytes and macrophages. To define the proximal promoter, the full 5'-sequence and transcriptional start sites of TLR2 mRNA were determined. The human TLR2 gene was found to consist of two 5' noncoding exons followed by a third coding exon. Alternative splicing of exon II was detected primarily in human blood monocytes. The proximal promoter, exon I, and part of intron I were found to be located in a CpG island. Although CpG methylation of the proximal human TLR2 promoter in cell lines correlated with TLR2 repression, the promoter was unmethylated in primary cells, indicating that CpG methylation does not contribute to the cell-type specific expression of human TLR2 in normal tissues. The promoter sequence contains putative binding sites for several transcription factors, including Sp1 and Ets family members. Reporter gene analysis revealed a minimal promoter of 220 bp that was found to be regulated by Sp1, Sp3, and possibly PU.1. Interestingly, no sequence homology was detected between human and murine TLR2 promoter regions. In contrast to murine TLR2, expression of human TLR2 in monocytes/macrophages is not induced by the proinflammatory stimuli LPS or macrophage-activating lipopeptide-2, and reporter activity of the promoter was not enhanced by stimuli-induced NF-kappaB activation in THP-1 or MonoMac-6 cells. Our findings provide an initial definition of the human TLR2 promoter and reveal profound differences in the regulation of an important pattern recognition molecule in humans and mice.


Hyperhidrosis Prevalence and Demographical Characteristics in Dermatology Outpatients in Shanghai and Vancouver.
There is a wide variation in the reported prevalence of primary hyperhidrosis in the literature. Further, it is unknown if primary hyperhidrosis is a lifelong condition, or if demographical factors influence hyperhidrosis prevalence. This study aims to examine the prevalence of hyperhidrosis in multiple ethnic groups from two ethnically diverse cities and to determine if the prevalence of primary hyperhidrosis changes according to age, gender, ethnicity, body mass index, and geographical locations. In total, 1010 consecutive subjects attending dermatology outpatient clinics in Shanghai Skin Disease Hospital and 1018 subjects in Skin Care Center of Vancouver General Hospital were invited to fill out a questionnaire on their presenting concerns, demographical information, and sweating symptoms. The subjects were then classified to have primary hyperhidrosis using the criteria of International Hyperhidrosis Society, late-onset hyperhidrosis, or no-hyperhidrosis. The prevalence of primary HH and late-onset HH was calculated for the entire study population and in subgroups stratified according to age of examination, sex, ethnicity, presenting diagnosis, body mass index, and specific study cities. Multivariate logistic regression analyses were performed to assess the impact of these factors on HH prevalence. The prevalence of primary hyperhidrosis is very similar in Shanghai and in Vancouver, at 14.5% and 12.3% respectively. In addition, 4.0% of subjects in Shanghai and 4.4% subjects in Vancouver suffer from late-onset HH. Primary HH has highest prevalence in those younger than 30 years of age, decreasing dramatically in later years. Caucasian subjects are at least 2.5 times more likely to develop axillary hyperhidrosis compared to Chinese subjects. Obesity does not have much influence on primary HH presentation, although it does increase significantly the development of late-onset HH. Finally, there is no major difference of hyperhidrosis between Chinese subjects in Shanghai and Vancouver. The data were gathered according to patients' self-reports only and the sample size was relatively small in some groups after stratification for gender, ethnicity and age. Prevalence of primary HH and late-onset HH is similar in dermatology outpatients independent of geographical locations. However, certain specific HH subtypes can show great variations according to ethnicity, age, body mass index and sex.


Efficacy and toxicity of gemcitabine and pegylated liposomal Doxorubicin in recurrent platinum-resistant/refractory epithelial ovarian cancer.
Treatment of patients with platinum resistant/refractory ovarian cancer is a significant problem. In this study, we evaluated the efficacy and tolerability of the combination of gemcitabine and pegylated liposomal doxorubicin (PLD) in patients with platinum resistant/refractory ovarian cancer. We retrospectively evaluated the activity and toxicity of gemcitabine and PLD combination in 35 patients with recurrent platinum resistant/refractory ovarian cancer who had been treated and followed up in 7 centers in Turkey between December 2005 and June 2008. The patients received gemcitabine 1.000 mg/m(2) on day 1 and 8, and PLD 25 mg/m(2) on day 1 every 28 days. A total of 187 cycles (median, 6 cycles) were delivered. An objective response rate of 28,6 % (1 complete, 9 partial response) was achieved. Additionally, 16 patients (45.7 %) had disease stabilization. The median time-to-progression was 6 months (95 % confidence interval, 4-8) and the median overall survival was 17 months (95 % confidence interval, 12-22). Grade 3-4 hematologic toxicities were as follows: leucopenia (14.3%), neutropenia (8.6%), and anemia (2.9%). One febrile neutropenic episode (2.9%) was observed. Non-hematologic toxicity was well tolerated and easily managed and no grade 3-4 palmoplantar erytrodysestesia (PPE) was observed. The combination of gemcitabine and PLD is an effective and tolerable treatment option, with 74.3 % disease control rate for patients with platinum resistant/refractory ovarian cancer.


Evaluation of T-cell responses to novel RD1- and RD2-encoded Mycobacterium tuberculosis gene products for specific detection of human tuberculosis infection.
The tuberculin skin test for diagnosing Mycobacterium tuberculosis infection suffers from antigenic cross-reactivity of purified protein derivative with BCG, resulting in poor specificity in BCG-vaccinated populations. Comparative genomics has identified several genetic regions in M. tuberculosis and M. bovis that are deleted in M. bovis BCG. Proteins encoded in these regions will form the basis of new specific T-cell-based blood tests that do not cross-react with BCG, but only two, early secretory antigen target 6 and culture filtrate protein 10, have been studied in detail in humans. We investigated four novel gene products, encoded by RD2 (Rv1989c) and RD1 (Rv3873, Rv3878, and Rv3879c), that are absent from most or all of the vaccine strains of BCG, respectively. Sixty-seven overlapping peptides were tested in ex vivo gamma interferon enzyme-linked immunospot assays in 49 patients with culture-confirmed tuberculosis and 38 healthy BCG-vaccinated donors. Forty-five percent (95% confidence interval [CI], 31 to 57%) and 53% (95% CI, 39 to 67%) of the tuberculosis patients responded to Rv3879c and Rv3873, respectively, identifying these proteins as major M. tuberculosis T-cell antigens in humans, while 35 and 25% of the patients responded to Rv3878 and Rv1989c, respectively. Of the 38 BCG-vaccinated donors, 1 (2.6%) responded to peptides from Rv3878 and Rv3879c, 3 (7.9%) responded to Rv3873, and none responded to Rv1989c. Exclusion of cross-reactive peptides encoded in conserved motifs of Rv3873, a PPE family member, increased its specificity to 97.4%. The high specificity of Rv3879c peptides and nonconserved Rv3873 sequences, together with their moderate sensitivity in tuberculosis patients, identifies these peptides as candidates for inclusion in new T-cell-based tests for M. tuberculosis infection.


[HIV-related non-Hodgkin lymphoma in 45 patients; a retrospective analysis].
Non-Hodgkin lymphoma is seen in approximately 5% of patients with AIDS. In recent years, the incidence has increased due to an extension of the average lifespan of HIV-infected individuals. In this article we describe the histological and clinical features of 45 patients with HIV-related non-Hodgkin lymphoma seen at the Academic Medical Centre between 1984 and 1991. There were 43 men and 2 women with a median age of 40 years. Most patients had high-grade B-cell lymphoma; 85% had extranodal sites. Prognosis was poor: overall median survival was only 3.8 months. Twelve patients were treated with 3 or more courses of chemotherapy: their median survival was 8 months. In 7 of 12 patients a complete remission was obtained; their median survival was 18 months. A history of AIDS was a poor prognostic factor.


Tropomyosin isoforms and reagents.
Tropomyosins are rod-like dimers which form head-to-tail polymers along the length of actin filaments and regulate the access of actin binding proteins to the filaments.1 The diversity of tropomyosin isoforms, over 40 in mammals, and their role in an increasing number of biological processes presents a challenge both to experienced researchers and those new to this field. The increased appreciation that the role of these isoforms expands beyond that of simply stabilizing actin filaments has lead to a surge of reagents and techniques to study their function and mechanisms of action. This report is designed to provide a basic guide to the genes and proteins and the availability of reagents which allow effective study of this family of proteins. We highlight the value of combining multiple techniques to better evaluate the function of different tm isoforms and discuss the limitations of selected reagents. Brief background material is included to demystify some of the unfortunate complexity regarding this multi-gene family of proteins including the unconventional nomenclature of the isoforms and the evolutionary relationships of isoforms between species. Additionally, we present step-by-step detailed experimental protocols used in our laboratory to assist new comers to the field and experts alike.


Extracellular Onchocerca-derived small RNAs in host nodules and blood.
microRNAs (miRNAs), a class of short, non-coding RNA can be found in a highly stable, cell-free form in mammalian body fluids. Specific miRNAs are secreted by parasitic nematodes in exosomes and have been detected in the serum of murine and dog hosts infected with the filarial nematodes Litomosoides sigmodontis and Dirofilaria immitis, respectively. Here we identify extracellular, parasite-derived small RNAs associated with Onchocerca species infecting cattle and humans. Small RNA libraries were prepared from total RNA extracted from the nodule fluid of cattle infected with Onchocerca ochengi as well as serum and plasma from humans infected with Onchocerca volvulus in Cameroon and Ghana. Parasite-derived miRNAs were identified based on the criteria that sequences unambiguously map to hairpin structures in Onchocerca genomes, do not align to the human genome and are not present in European control serum. A total of 62 mature miRNAs from 52 distinct pre-miRNA candidates were identified in nodule fluid from cattle infected with O. ochengi of which 59 are identical in the genome of the human parasite O. volvulus. Six of the extracellular miRNAs were also identified in sequencing analyses of serum and plasma from humans infected with O. volvulus. Based on sequencing analysis the abundance levels of the parasite miRNAs in serum or plasma range from 5 to 127 reads/per million total host miRNA reads identified, comparable to our previous analyses of Schistosoma mansoni and L. sigmodontis miRNAs in serum. All six of the O. volvulus miRNAs identified have orthologs in other filarial nematodes and four were identified in the serum of mice infected with L. sigmodontis. We have identified parasite-derived miRNAs associated with onchocerciasis in cattle and humans. Our results confirm the conserved nature of RNA secretion by diverse nematodes. Additional species-specific small RNAs from O. volvulus may be present in serum based on the novel miRNA sequences identified in the nodule fluid. In our analyses comparison to European control serum illuminates the scope for false-positives, warranting caution in criteria that should be applied to identification of biomarkers of infection.


Cross-Linked Enzyme Aggregates as Versatile Tool for Enzyme Delivery: Application to Polymeric Nanoparticles.
Polymeric nanoparticles (NPs) represent one of the most promising tools in nanomedicine and have been extensively studied for the delivery of water-insoluble drugs. However, the efficient loading of therapeutic enzymes and proteins in polymer-based nanostructures remains an open challenge. Here, we report a synthesis method for a new enzyme delivery system based on cross-linked enzyme aggregates (CLEAs) encapsulation into poly(lactide- co-glycolide) (PLGA) NPs. We tested the encapsulation strategy on four enzymes currently investigated for enzyme replacement therapy: palmitoyl protein thioesterase 1 (PPT1; defective in NCL1 disease), galactosylceramidase (GALC; defective in globoid cell leukodystrophy), alpha glucosidase (aGLU; defective in Pompe disease), and beta glucosidase (bGLU; defective in Gaucher's disease). We demonstrated that our system allows encapsulation of enzymes with excellent activity retention (usually around 60%), thus leading to functional and targeted nanostructures suitable for enzyme delivery. We then demonstrated that CLEA NPs efficiently deliver PPT1 in cultured cells, with almost complete enzyme release occurring in 48 h. Finally, we demonstrated that enzymatic activity is fully recovered in primary NCL1 fibroblasts upon treatment with PPT1 CLEA NPs.


Sugar-Sweetened Beverage Consumption Is Adversely Associated with Childhood Attention Deficit/Hyperactivity Disorder.
Attention deficit/hyperactivity disorder (ADHD) is one of the most common childhood neurobehavioral conditions. Evidence of the negative effects of sugar-sweetened beverages (SSBs) on mental health has not been convincing, although a few studies have found an association between high SSB levels and attention problems in children. This study aimed to test the hypothesis that SSB consumption is associated with ADHD among children. Doctor-diagnosed ADHD cases (n = 173) and non-ADHD controls (n = 159) between age 4 to 15 were recruited. SSB consumption, socio-demographic and lifestyle characteristics of the children, as well as of their mothers' characteristics during pregnancy, were collected using a questionnaire. Blood lead levels and polymorphisms of two commonly verified dopaminergic-related genes (the D4 dopamine receptor gene DRD4 and the dopamine transporter gene DAT1) were also analyzed. There was a dose-response relationship between SSB consumption and ADHD. After covariates were adjusted, children who consumed SSBs at moderate levels and high levels had 1.36 and 3.69 odds, respectively, of having ADHD, compared with those who did not consume SSBs (p for trend < 0.05). Similar results were obtained when females were excluded. Our findings highlighted the adverse correlation between SSB consumption and ADHD and indicated a dose-response effect even after covariates were adjusted.


Effects of rilpivirine, 17β-estradiol and β-naphthoflavone on the inflammatory status of release of adipocytokines in 3T3-L1 adipocytes in vitro.
Rilpivirine is a non-nucleoside reverse transcriptase inhibitor, recently developed as a drug of choice for initial anti-retroviral (ARV) treatment of HIV-1 infection, whereas estradiol is a major component of hormonal contraceptives. Both drugs have effects on lipid metabolism, impairment of adipocyte differentiation and alteration of adipose tissue distribution and function.This study investigated the effects of different concentrations of either rilpivirine or estradiol either alone or in combination on adipocyte differentiation and adipocytokines status in vitro in the absence and presence of β-naphthoflavone, (BNF),a potent agonist of the aryl hydrocarbon receptor. 3T3-L1 human pre-adipocytes were cultured and differentiated with different concentrations of treatment drugs. After 10 days of differentiation procedure, cells were examined for their morphology and viability. Glycerol,adiponectin, leptin, resistin and interleukin-8 (IL-8) were quantified using commercially available kits. The results show that either rilpivirine or estradiol individually or during their combination can evoke significant increases in glycerol release and a concomitant significant decrease of adiponectin from adipocytes. These effects were dose-dependent. The effects of combined treatments were much larger than individual concentration for each drug. Both drugs had little of no effect on leptin levels, except for a small decrease with 10 µM rilpivirine alone or when combined with estradiol. In addition, both drugs evoked small increases in the release of resistin and interleukin-8 with significant values at higher doses compared to untreated adipocytes.When adipocytes were pretreated with BNF, either rilpivirine or, estradiol or when combined evoked a much larger release in glycerol and a much larger decrease in adiponectin compared to the absence of BNF. In contrast, BNF pretreatment had little of no effect on either leptin, resistin or IL-8 metabolism compared to the results obtained in the presence of either rilpivirine or estradiol alone or in combination.These results show that rilpivirine and estradiol either alone or when combined or pretreated with BNF can evoke marked effects on glycerol and cytokines levels from adipocytes. However, their mechanism (s) in inducing adipogenesis warrants further investigation of different transcription factors at gene expression levels.


Proteolytic cleavage of the Fe-S subunit hinge region of Rhodobacter capsulatus bc(1) complex: effects of inhibitors and mutations.
The three-dimensional structure of the mitochondrial bc(1) complex reveals that the extrinsic domain of the Fe-S subunit, which carries the redox-active [2Fe2S] cluster, is attached to its transmembrane anchor domain by a short flexible hinge sequence (amino acids D43 to S49 in Rhodobacter capsulatus). In various structures, this extrinsic domain is located in different positions, and the conformation of the hinge region is different. In addition, proteolysis of this region has been observed previously in a bc(1) complex mutant of R. capsulatus [Saribas, A. S., Valkova-Valchanova, M. B., Tokito, M., Zhang, Z., Berry E. A., and Daldal, F. (1998) Biochemistry 37, 8105-8114]. Thus, possible correlations between proteolysis, conformation of the hinge region, and position of the extrinsic domain of the Fe-S subunit within the bc(1) complex were sought. In this work, we show that thermolysin, or an endogenous activity present in R. capsulatus, cleaves the hinge region of the Fe-S subunit between its amino acid residues A46-M47 or D43-V44, respectively, to yield a protease resistant fragment with a M(r) of approximately 18 kDa. The cleavage was affected significantly by ubihydroquinone oxidation (Q(o)) and ubiquinone reduction (Q(i)) site inhibitors and by specific mutations located in the bc(1) complex. In particular, using either purified or detergent dispersed chromatophore-embedded R. capsulatus bc(1) complex, we demonstrated that while stigmatellin blocked the cleavage, myxothiazol hardly affected it, and antimycin A greatly enhanced it. Moreover, mutations in various regions of the Fe-S subunit and cyt b subunit changed drastically proteolysis patterns, indicating that the structure of the hinge region of the Fe-S subunit was modified in these mutants. The overall findings establish that protease accessibility of the Fe-S subunit of the bc(1) complex is a useful biochemical assay for probing the conformation of its hinge region and for monitoring indirectly the position of its extrinsic [2Fe2S] cluster domain within the Q(o) pocket.


Racial/ethnic disparities in service utilization for individuals with co-occurring mental health and substance use disorders in the general population: results from the national epidemiologic survey on alcohol and related conditions.
This study sought to determine whether black/white disparities in service utilization for mental health and substance use disorders persist or are diminished among individuals with psychiatric comorbidity in the general population. The 2001-2002 National Epidemiologic Survey on Alcohol and Related Conditions was used to identify individuals with lifetime co-occurring substance use disorders and mood/anxiety disorders (N = 4250; whites, N = 3597; blacks, N = 653). Lifetime service utilization for problems with mood, anxiety, alcohol, and drugs was assessed. Compared to whites, blacks with co-occurring mood or anxiety and substance use disorders were significantly less likely to receive services for mood or anxiety disorders, equally likely to receive services for alcohol use disorders, and more likely to receive some types of services for drug use disorders. Regardless of race/ethnicity, individuals with these co-occurring disorders were almost twice as likely to use services for mood/anxiety disorders than for substance use disorders. Despite the fact that comorbidity generally increases the likelihood of service use, black/white disparities in service utilization among an all-comorbid sample were found, although these disparities differed by type of disorder. Further research is warranted to understand the factors underlying these differences. Prevention and intervention strategies are needed to address the specific mental health needs of blacks with co-occurring disorders, as well as the overall lack of service use for substance use disorders among individuals with co-occurring psychiatric conditions.